The metabolism of salicylidene benzylamine, a pro-drug for salicylate, in rats and dogs

Abstract

1. Oral doses of [¹⁴C]salicylidene benzylamine were well absorbed by rats and dogs and excreted mainly in the urine (92% dose by rat in 24 h and 84% by dog in 48 h).

2. After 50,100 and 300 mg/kg oral doses to rats, peak mean plasma ¹⁴C concn. (mainly salicylic acid) of 77,243 and 396 μg equiv./ml respectively were reached between 2 and 4 h and maintained at this level until about 7.5 h. ¹⁴C was cleared more rapidly from the plasma of male rats than from that of female rats. After 44, 85 and 300 mg/kg oral doses to dogs, peak mean plasma ¹⁴C concn. (mainly salicylic acid) of 114, 194 and 320 μg equiv. ml respectively were reached at 4 h and then declined with a half-life of 6–7 h.

3. Tissue ¹⁴C concn. in both species were greatest at the times of peak plasma ¹⁴C concn., but in general were lower than those in the corresponding plasma.

4. The major components in rat and dog urine were salicyl alcohol, salicylic acid and salicyluric acid, the first two being excreted partly as glucuronic acid/sulphate conjugates. After initial hydrolysis of salicylidene benzylamine to salicylaldehyde, approximately equal amounts were reduced and oxidized to the corresponding alcohol and acid respectively.